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HISTORICAL PERSPECTIVE OF GASTROESOPHAGEAL REFLUX DISEASE CLINICAL TREATMENT.
Zaterka, S, Marion, SB, Roveda, F, Perrotti, MA, Chinzon, D
Arquivos de gastroenterologia. 2019;(2):202-208
Abstract
BACKGROUND Gastroesophageal reflux disease (GERD) is one of the most prevalent gastrointestinal diseases. GERD generates significant impairment in patients' quality of life and it is associated to relevant medical resources utilization. A better understanding of GERD pathophysiology in the past five decades has favored the evolution of therapeutic strategies from non-drug interventions and antacids to more efficacious and safer alternatives. OBJECTIVE To summarize data about the historical evolution of GERD management in Brazil, focusing on medical therapy and addressing evidence on efficacy and safety of drug classes currently recommended. METHODS A narrative review was conducted by systematizing information about discoveries on GERD pathophysiology. We also addressed efficacy and safety of medications currently used to reduce symptoms and improve endoscopic healing of esophageal lesions. A structured search on Pubmed was performed to identify systematic reviews and meta-analysis investigating GERD outcomes positively impacted by proton pump inhibitors (PPIs), the first choice of pharmacotherapy for the disease. RESULTS The chronological development of therapeutic measures for GERD in Brazil evolved from lifestyle interventions with relative poor effect on symptoms related to esophageal acid exposure, particularly heartburn, to effective and safe pharmacological interventions such as histamine H2-receptor antagonists and PPIs. In the present days, some drug classes play a minor role in disease management, namely prokinetics and antacids, due to their reduced efficacy and relevant safety concerns (particularly with prokinetics). The main challenge for prescribers and researchers seems to be finding long-acting acid suppressants strategies able to ameliorate patients' symptoms and quality of life, thereafter, reducing medical resource consumption. The dual delayed-release PPI dexlansoprazole seems to respond for some of the limitations other PPIs have. CONCLUSION Recognizing the historical evolution of GERD management can help care providers to better understand therapeutic options for their patients, as well as focus on unmet needs that deserve further attention. PPIs are still the first choice therapy, with good evidence in favor of their efficacy, despite some safety concerns. However, as with any medical intervention, it is recommended to prescribe PPIs for patients with clear indication, using adequate dosing and monitoring for adverse events.
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What is the long term acid inhibitor treatment in gastroesophageal reflux disease? What are the potential problems related to long term acid inhibitor treatment in gastroesophageal reflux disease? How should these cases be followed?
Hatemi, İ, Esatoğlu, SN
The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology. 2017;(Suppl 1):S57-S60
Abstract
The meta-analyses of observational studies (OBS) showed the risk of any fracture and hip fracture slightly increased with proton pump inhibitor (PPI) treatment depending on the dose and regardless of time. This was not observed with histamine-2 receptor antagonists (H2RA). The risk of bacterial overgrowth and spontaneous bacterial peritonitis were increased with PPI therapy, but not with H2RA. In meta-analyses of OBS, a slight increase was observed in the risk of community-acquired pneumonia (CAP) in the early stages (<1 month) of PPI use and particularly at high doses. In a five-year LOTUS study, no difference was found in vitamin B12, folic acid, vitamin D, and calcium values in terms of the initial and end of follow-up levels. No increase in the risk of premalignant gastric lesions was observed in the meta-analysis of RCTs in which PPI treatment (≥6 months) was given to Helicobacter pylori negative patients. The risk of hypomagnesemia with PPI use was increased in patients having GFR<60, using diuretics, and over 65 years of age. Quasi-experimental studies showed a reduced zinc absorption with PPI use. In the meta-analysis of OBS, long-term (>1 year) PPI use increased the risk of fundic polyps, but no risk was found in shorter use. The meta-analyses of RCTS showed no difference between PPI and surgery or placebo arms and between the arms of H2RA and placebo in terms of all side effects. No difference was found between the PPI and H2RA arms both in all and serious adverse effects.
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A Review of the Novel Application and Potential Adverse Effects of Proton Pump Inhibitors.
Yu, LY, Sun, LN, Zhang, XH, Li, YQ, Yu, L, Yuan, ZQ, Meng, L, Zhang, HW, Wang, YQ
Advances in therapy. 2017;(5):1070-1086
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Abstract
Proton pump inhibitors (PPIs) are known as a class of pharmaceutical agents that target H+/K+-ATPase, which is located in gastric parietal cells. PPIs are widely used in the treatment of gastric acid-related diseases including peptic ulcer disease, erosive esophagitis and gastroesophageal reflux disease, and so on. These drugs present an excellent safety profile and have become one of the most commonly prescribed drugs in primary and specialty care. Except for gastric acid-related diseases, PPIs can also be used in the treatment of Helicobacter pylori infection, viral infections, respiratory system diseases, cancer and so on. Although PPIs are mainly used short term in patients with peptic ulcer disease, nowadays these drugs are increasingly used long term, and frequently for a lifetime, for instance in patients with typical or atypical symptoms of gastroesophageal reflux disease and in NSAID or aspirin users at risk of gastrotoxicity and related complications including hemorrhage, perforation and gastric outlet obstruction. Long-term use of PPIs may lead to potential adverse effects, such as osteoporotic fracture, renal damage, infection (pneumonia and clostridium difficile infection), rhabdomyolysis, nutritional deficiencies (vitamin B12, magnesium and iron), anemia and thrombocytopenia. In this article, we will review some novel uses of PPIs in other fields and summarize the underlying adverse reactions.
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Which drugs are risk factors for the development of gastroesophageal reflux disease?
Mungan, Z, Pınarbaşı Şimşek, B
The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology. 2017;(Suppl 1):S38-S43
Abstract
Gastroesophageal reflux disease (GERD), which is common in many communities, is associated with structural factors, eating habits, and the use of certain drugs. The use of such drugs can lead to the emergence of GERD and can also exacerbate existing reflux symptoms. These drugs can contribute to GERD by directly causing mucosal damage, by reducing lower esophageal sphincter pressure (LESP), or by affecting esophagogastric motility. In this article, we report our investigation of the relationships between GERD and medications within the scope of the "Turkish GERD Consensus Group." For the medication groups for which sufficient data were obtained (Figure 1), a systematic literature review in English was conducted using the keywords "gastroesophageal reflux" [MeSH Terms] and "anti-inflammatory agents, non-steroidal" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "acetylsalicylic acid" [MeSH Terms], "gastroesophageal reflux" [All Fields] and "estrogenic agents" [All Fields], "gastroesophageal reflux" [All Fields] and "progesterones" [All Fields], "gastroesophageal reflux" [All Fields] and "hormone replacement therapy" [All Fields], "gastroesophageal reflux" [MeSH Terms] and "diphosphonates" [MeSH Terms] OR "diphosphonates" [All Fields], "calcium channel blockers" [MeSH Terms] and "gastroesophageal reflux" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "nitrates" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "antidepressive agents" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "benzodiazepines" [MeSH Terms] and "hypnotic drugs" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "cholinergic antagonists" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "theophylline" [MeSH Terms], and "gastroesophageal reflux [MeSH Terms] AND "anti-asthmatic agents" [MeSH Terms]. The studies were analyzed and the results are presented here.
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Metabolic and nutritional complications of bariatric surgery : a review.
Mesureur, L, Arvanitakis, M
Acta gastro-enterologica Belgica. 2017;(4):515-525
Abstract
Bariatric surgery is considered as the only effective durable weight-loss therapy and may be curative for obesity-related comorbidities such as diabetes. Nevertheless this surgery is not devoid of potential long-term complications such as dumping syndrome, gastroesophageal reflux disease and nutrient deficiencies. For this reason, preoperative nutritional assessment and rigorous postoperative follow-up with administration of multi-vitamins supplements and assessment of serum levels is recommended for each patient who is undergoing a bariatric surgery. The aim of this review is to identify and treat the metabolic and nutritional complications of bariatric surgery.
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Pharmacological treatment of children with gastro-oesophageal reflux.
Tighe, M, Afzal, NA, Bevan, A, Hayen, A, Munro, A, Beattie, RM
The Cochrane database of systematic reviews. 2014;(11):CD008550
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Abstract
BACKGROUND Gastro-oesophageal reflux (GOR) is a common disorder, characterised by regurgitation of gastric contents into the oesophagus. GOR is a very common presentation in infancy in both primary and secondary care settings. GOR can affect approximately 50% of infants younger than three months old (Nelson 1997). The natural history of GOR in infancy is generally that of a functional, self-limiting condition that improves with age; < 5% of children with vomiting or regurgitation continue to have symptoms after infancy (Martin 2002). Older children and children with co-existing medical conditions can have a more protracted course. The definition of gastro-oesophageal reflux disease (GORD) and its precise distinction from GOR are debated, but consensus guidelines from the North American Society of Gastroenterology, Hepatology and Nutrition (NASPGHAN-ESPGHAN guidelines 2009) define GORD as 'troublesome symptoms or complications of GOR.' OBJECTIVES This Cochrane review aims to provide a robust analysis of currently available pharmacological interventions used to treat children with GOR by assessing all outcomes indicating benefit or harm. SEARCH METHODS We sought to identify relevant published trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 5), MEDLINE and EMBASE (1966 to 2014), the Centralised Information Service for Complementary Medicine (CISCOM), the Institute for Scientific Information (ISI) Science Citation Index (on BIDS-UK General Science Index) and the ISI Web of Science. We also searched for ongoing trials in the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com).Reference lists from trials selected by electronic searching were handsearched for relevant paediatric studies on medical treatment of children with gastro-oesophageal reflux, as were published abstracts from conference proceedings (published in Gut and Gastroenterology) and reviews published over the past five years.No language restrictions were applied. SELECTION CRITERIA Abstracts were reviewed by two review authors, and relevant RCTs on study participants (birth to 16 years) with GOR receiving a pharmacological treatment were selected. Subgroup analysis was considered for children up to 12 months of age, and for children 12 months to 16 years of age, and for those with neurological impairment. DATA COLLECTION AND ANALYSIS Trials were critically appraised and data collected by two review authors. Risk of bias was assessed. Meta-analysis data were independently extracted by two review authors, and suitable outcome data were analysed using RevMan. MAIN RESULTS A total of 24 studies (1201 participants) contributed data to the review. The review authors had several concerns regarding the studies. Pharmaceutical company support for manuscript preparation was a common feature; also, because common endpoints were lacking, study populations were heterogenous and variations in study design were noted, individual drug meta-analysis was not possible.Moderate-quality evidence from individual studies suggests that proton pump inhibitors (PPIs) can reduce GOR symptoms in children with confirmed erosive oesophagitis. It was not possible to demonstrate statistical superiority of one PPI agent over another.Some evidence indicates that H₂antagonists are effective in treating children with GORD. Methodological differences precluded performance of meta-analysis on individual agents or on these agents as a class, in comparison with placebo or head-to-head versus PPIs, and additional studies are required.RCT evidence is insufficient to permit assessment of the efficacy of prokinetics. Given the diversity of study designs and the heterogeneity of outcomes, it was not possible to perform a meta-analysis of the efficacy of domperidone.In younger children, the largest RCT of 80 children (one to 18 months of age) with GOR showed no evidence of improvement in symptoms and 24-hour pH probe, but improvement in symptoms and reflux index was noted in a subgroup treated with domperidone and co-magaldrox(Maalox(®) ). In another RCT of 17 children, after eight weeks of therapy. 33% of participants treated with domperidone noted an improvement in symptoms (P value was not significant). In neonates, the evidence is even weaker; one RCT of 26 neonates treated with domperidone over 24 hours showed that although reflux frequency was significantly increased, reflux duration was significantly improved.Diversity of RCT evidence was found regarding efficacy of compound alginate preparations(Gaviscon Infant(®) ) in infants, although as a result of these studies, Gaviscon Infant(®) was changed to become aluminium-free and has been assessed in its current form in only two studies since 1999. Given the diversity of study designs and the heterogeneity of outcomes, as well as the evolution in formulation, it was not possible to perform a meta-analysis on the efficacy of Gaviscon Infant(®) . Moderate evidence indicates that Gaviscon Infant(®) improves symptoms in infants, including those with functional reflux; the largest study of the current formulation showed improvement in symptom control but was limited by length of follow-up.No serious side effects were reported.No RCTs on pharmacological treatments for children with neurodisability were identified. AUTHORS' CONCLUSIONS Moderate evidence was found to support the use of PPIs, along with some evidence to support the use of H₂ antagonists in older children with GORD, based on improvement in symptom scores, pH indices and endoscopic/histological appearances. However, lack of independent placebo-controlled and head-to-head trials makes conclusions as to relative efficacy difficult to determine. Further RCTs are recommended. No robust RCT evidence is available to support the use of domperidone, and further studies on prokinetics are recommended, including assessments of erythromycin.Pharmacological treatment of infants with reflux symptoms is problematic, as many infants have GOR, and little correlation has been noted between reported symptoms and endoscopic and pH findings. Better evidence has been found to support the use of PPIs in infants with GORD, but heterogeneity in outcomes and in study design impairs interpretation of placebo-controlled data regarding efficacy. Some evidence is available to support the use of Gaviscon Infant(®) , but further studies with longer follow-up times are recommended. Studies of omeprazole and lansoprazole in infants with functional GOR have demonstrated variable benefit, probably because of differences in inclusion criteria.No robust RCT evidence has been found regarding treatment of preterm babies with GOR/GORD or children with neurodisabilities. Initiation of RCTs with common endpoints is recommended, given the frequency of treatment and the use of multiple antireflux agents in these children.
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Eosinophilic oesophagitis: from physiopathology to treatment.
Roman, S, Savarino, E, Savarino, V, Mion, F
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2013;(11):871-8
Abstract
Eosinophilic oesophagitis is a chronic inflammatory disease characterized by eosinophilic infiltration of the oesophageal mucosa. Food and aero-allergens are involved in its pathogenesis. Dysphagia and food impaction are the dominant symptoms in adult with eosinophilic oesophagitis. However, a wide range of symptoms has been noticed such as chest pain or gastro-oesophageal reflux disease-like symptoms. Upper gastro-intestinal endoscopy and oesophageal biopsies are crucial for the diagnosis of eosinophilic oesophagitis. Endoscopy might be normal or reveal typical patterns such as rings, furrows, exudates, oedema, and stricture. Two to four biopsies should be performed both in the distal and in the proximal oesophagus, and 15 eosinophils per high power field within the oesophageal epithelium are the minimal threshold to diagnose eosinophilic oesophagitis. Allergy testing is recommended, although its impact to orient treatment remains to be demonstrated. Eosinophilic oesophagitis treatment includes medical treatment, diet and endoscopic dilation. Proton pump inhibitors are the first-line therapy as some eosinophilic oesophagitis phenotypes respond well to proton pump inhibitors. Topical viscous corticosteroids or diet elimination are the treatment of choice. There is no clear evidence in the literature to prefer one to the other. Finally endoscopic dilation should be considered in case of persistent symptomatic stenosis despite medical therapy.
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[Obesity and functional gastrointestinal disorders].
Lee, KJ
The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi. 2012;(1):1-7
Abstract
Obesity is prevalent in Korea. An increase in food intake and a decrease in energy expenditure are responsible for obesity. Gut hormones play a role in controlling food intake. Obesity is suggested to be linked to common gastrointestinal functional disorders. Obesity is associated with an increased risk of gastroesophageal reflux disease, Barrett esophagus and esophageal adenocarcinoma. Epidemiologic studies indicate that obesity is associated with chronic gastrointestinal symptoms. This association suggests the possibility that obesity and functional gastrointestinal disorders may be pathophysiologically linked. However, data on the relationship between obesity and functional gastrointestinal disorders are inconsistent. In this paper, we review the role of gastrointestinal hormones in food intake and the relationship between obesity and functional gastrointestinal disorders.
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Esophageal impedance monitoring for gastroesophageal reflux.
Mousa, HM, Rosen, R, Woodley, FW, Orsi, M, Armas, D, Faure, C, Fortunato, J, O'connor, J, Skaggs, B, Nurko, S
Journal of pediatric gastroenterology and nutrition. 2011;(2):129-39
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Abstract
Dual pH-multichannel intraluminal impedance (pH-MII) is a sensitive tool for evaluating overall gastroesophageal reflux disease, and particularly for permitting detection of nonacid reflux events. pH-MII technology is especially useful in the postprandial period or at other times when gastric contents are nonacidic.pH-MII was recently recognized by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition as being superior to pH monitoring alone for evaluation of the temporal relation between symptoms and gastroesophageal reflux. In children, pH-MII is useful to correlate symptoms with reflux (particularly nonacid reflux), to quantify reflux during tube feedings and the postprandial period, and to assess efficacy of antireflux therapy. This clinical review is simply an evidence-based overview addressing the indications, limitations, and recommended protocol for the clinical use of pH-MII in children.
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[Scientific foundations for medical treatment based on modifying diet, lifestyle habits, and patient attitudes in chronic gastroesophageal reflux disease].
Csendes, A, Burdiles, P
Cirugia espanola. 2007;(2):64-9
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Abstract
In most patients with chronic gastroesophageal reflux disease, treatment is medical. Among the main elements involved in treatment are general dietary measures, lifestyle habits, and patients' attitudes to symptom control. The present article summarizes the scientific foundations that support these measures: head elevation during nighttime sleep, smoking cessation, losing weight, avoiding rigorous exercise, and reducing or eliminating alcohol consumption. Dietary therapy is mainly based on avoiding fatty foods, chocolate, coffee, mint, and irritating fizzy drinks. Although each patient's response to these measures is highly individual, the mechanisms through which symptoms are reproduced is gradually becoming clearer: a large percentage of patients with uncomplicated gastroesophageal reflux disease will gain considerable relief simply by eliminating some of these habits.